FUNCTIONAL GENOMICS OF A DEAFNESS/BLINDNESS SYNDROME
(2002)
Abstract :
DESCRIPTION: The gene responsible for Usher Syndrome Type 1C, an autosomal recessively inherited deafness/blindness syndrome, was previously mapped by genetic linkage analysis between the markers D11S861 and 899. The major focus of this proposal is to clone, and characterize the USH1C gene and its product, providing critical information on the underlying pathophysiological mechanism for this and other forms of dual neurosensory syndromes. Since this region was found to be refractory to cloning using YAC (yeast artificial chromosome) based vectors, a P1-artificial -chromosome (PAC) contig was constructed. The 400 kb contig encompassing the critical region is providing the genomic resources for a gene hunt using exon trapping, cDNA selection, and direct sequencing. We are currently investigating several new transcription units which we have identified and mapped into the critical region. The current proposal is directed at (1) identifying transcription units in the critical region; (2) analyzing cDNAs to determine which represent intriguing candidate genes; (3) examining patient DNA for mutations by sequencing to identify the gene, and; (4) characterizing the gene and its product at the tissue and cellular levels. Since the phenotype for Usher type 1C is indistinguishable with the other five USH1 loci, this study may yield insights into the mechanism responsible for profound deafness, vestibular dysfunction and progressive retinal degeneration and provide new insights into the syndrome responsible for the majority of children born with dual neurosensory degeneration.
| Project Number : | 5R01DC003697-03 |
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| ICD : | NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS |
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| IRG : | HAR |
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| Project Terms : | blindness, congenital deafness, developmental genetics, genetic disorder, retinitis pigmentosa complementary DNA, gene induction /repression, gene mutation, genetic transcription, neurogenetics, nucleic acid sequence, transcription factor animal genetic material tag, embryo /fetus cell culture, human fetus tissue, human genetic material tag, laboratory mouse, molecular cloning |
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TUMOR SUPPRESSORS AND IMPRINTING AT CHROMOSOME 11P155
(2001)
Abstract :
DESCRIPTION (Adapted from investigator's abstract): Loss of heterozygosity (LOH) in pediatric and adult tumors indicates that chromosome band 11p15.5 harbors one or more growth or tumor suppressor genes. This notion is supported by growth arrest and tumor suppression studies using RD and G401 cell hybrid functional assays. In addition, the genes responsible for Beckwith-Wiedemann syndrome (BWS; an overgrowth and cancer predisposition disorder) and Long QT syndrome map to this region. The applicants have isolated this important region in PAC clones generating a 1l0-1.1 mb contig between D11S601 and IGF2/H19. They have located nine known genes in this contig and identified 18 novel transcripts. Tissue specific expression patterns of these novel genes have been determined by northern blotting. Since this region is imprinted, allele-specific expression is being assessed by conventional methods as well as a novel somatic cell hybrid assay. Two novel genes (one of which is imprinted) are overlapping and divergently transcribed, and exhibit their highest level of expression in fetal and adult liver and kidney making them candidates for tumor suppressors in hepatoblastoma and Wilms' tumor. Three BWS rearrangement breakpoints and a rhabdoid tumor breakpoint have been shown to disrupt the Long QT (KVLQT1) gene. The applicants also show that one of these rearrangements is associated with relaxation of genomic imprinting at IGF2 and recognition of a novel differentially methylated CpG-island. Studies are proposed to characterize 11p15.5 novel genes with respect to their expression in tumors. Those genes exhibiting an appropriate expression profile will be screened for mutations in Wilms' tumor, rhabdomyosarcomas and breast and ovarian carcinomas The tumor suppressor potential of candidate genes will be tested in a functional assay by expressing them in RD and G401 cells. Studies are also proposed to identify epigenetic changes in tumors and BWS patients as well as to identify a 11p15 imprinting cancer (IC). These studies will further our understanding of the molecular pathology of cancer including the involvement of genomic imprinting. This information may identify valuable prognostic markers and will facilitate more rational approaches to cancer therapies.
| Project Number : | 2R01CA063333-04A1 |
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| ICD : | NATIONAL CANCER INSTITUTE |
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| IRG : | MGN |
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| Project Terms : | gene mutation, genomic imprinting, molecular oncology, neoplasm /cancer genetics, restriction mapping, tumor suppressor gene Wilms' tumor, breast neoplasm, chromosome aberration, gene rearrangement, genetic marker, loss of heterozygosity, nucleic acid sequence, ovary neoplasm, restriction fragment length polymorphism, rhabdomyosarcoma artificial chromosome, fluorescent in situ hybridization, human genetic material tag, human tissue, hybrid cell, in situ hybridization, molecular cloning, polymerase chain reaction, single strand conformation polymorphism, southern blotting |
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FUNCTIONAL GENOMICS OF A DEAFNESS/BLINDNESS SYNDROME
(2001)
Abstract :
DESCRIPTION: The gene responsible for Usher Syndrome Type 1C, an autosomal recessively inherited deafness/blindness syndrome, was previously mapped by genetic linkage analysis between the markers D11S861 and 899. The major focus of this proposal is to clone, and characterize the USH1C gene and its product, providing critical information on the underlying pathophysiological mechanism for this and other forms of dual neurosensory syndromes. Since this region was found to be refractory to cloning using YAC (yeast artificial chromosome) based vectors, a P1-artificial -chromosome (PAC) contig was constructed. The 400 kb contig encompassing the critical region is providing the genomic resources for a gene hunt using exon trapping, cDNA selection, and direct sequencing. We are currently investigating several new transcription units which we have identified and mapped into the critical region. The current proposal is directed at (1) identifying transcription units in the critical region; (2) analyzing cDNAs to determine which represent intriguing candidate genes; (3) examining patient DNA for mutations by sequencing to identify the gene, and; (4) characterizing the gene and its product at the tissue and cellular levels. Since the phenotype for Usher type 1C is indistinguishable with the other five USH1 loci, this study may yield insights into the mechanism responsible for profound deafness, vestibular dysfunction and progressive retinal degeneration and provide new insights into the syndrome responsible for the majority of children born with dual neurosensory degeneration.
| Project Number : | 1R01DC003697-01 |
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| ICD : | NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS |
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| IRG : | HAR |
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| Project Terms : | blindness, congenital deafness, developmental genetics, genetic disorder, retinitis pigmentosa complementary DNA, gene induction /repression, gene mutation, genetic transcription, neurogenetics, nucleic acid sequence, transcription factor animal genetic material tag, embryo /fetus cell culture, human embryo /fetus tissue, human genetic material tag, laboratory mouse, molecular cloning |
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FUNCTIONAL GENOMICS OF A DEAFNESS/BLINDNESS SYNDROME
(2001)
Abstract :
DESCRIPTION: The gene responsible for Usher Syndrome Type 1C, an autosomal recessively inherited deafness/blindness syndrome, was previously mapped by genetic linkage analysis between the markers D11S861 and 899. The major focus of this proposal is to clone, and characterize the USH1C gene and its product, providing critical information on the underlying pathophysiological mechanism for this and other forms of dual neurosensory syndromes. Since this region was found to be refractory to cloning using YAC (yeast artificial chromosome) based vectors, a P1-artificial -chromosome (PAC) contig was constructed. The 400 kb contig encompassing the critical region is providing the genomic resources for a gene hunt using exon trapping, cDNA selection, and direct sequencing. We are currently investigating several new transcription units which we have identified and mapped into the critical region. The current proposal is directed at (1) identifying transcription units in the critical region; (2) analyzing cDNAs to determine which represent intriguing candidate genes; (3) examining patient DNA for mutations by sequencing to identify the gene, and; (4) characterizing the gene and its product at the tissue and cellular levels. Since the phenotype for Usher type 1C is indistinguishable with the other five USH1 loci, this study may yield insights into the mechanism responsible for profound deafness, vestibular dysfunction and progressive retinal degeneration and provide new insights into the syndrome responsible for the majority of children born with dual neurosensory degeneration.
| Project Number : | 5R01DC003697-02 |
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| ICD : | NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS |
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| IRG : | HAR |
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| Project Terms : | blindness, congenital deafness, developmental genetics, genetic disorder, retinitis pigmentosa complementary DNA, gene induction /repression, gene mutation, genetic transcription, neurogenetics, nucleic acid sequence, transcription factor animal genetic material tag, embryo /fetus cell culture, human embryo /fetus tissue, human genetic material tag, laboratory mouse, molecular cloning |
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MAPPING HUMAN GENES AND ASSOCIATED DISEASES
(1998)
| Project Number : | 5R01HG000333-24 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | GNM |
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CLONING RETINAL GENES LOCATED ON CHROMOSOME 11
(1998)
| Project Number : | 5R01EY010514-03 |
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| ICD : | NATIONAL EYE INSTITUTE |
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| IRG : | VISC |
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CLONING CHROMOSOME 11 GENES INVOLVED IN NEOPLASIA
(1998)
| Project Number : | 5R01CA063333-03 |
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| ICD : | NATIONAL CANCER INSTITUTE |
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| IRG : | MGN |
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CLONING RETINAL GENES LOCATED ON CHROMOSOME 11
(1997)
Abstract :
Genes coding for inherited eye disorders have been mapped by family studies and genetic linkage tests to two specific regions (11 q13 and 11p14/15.1) on human chromosome 11. The aim of this proposal is to locate and clone these genes associated with impaired sight. This will be accomplished by generating an ordered overlapping clone map consisting of chromosome ii specific YAC (yeast artificial chromosome) clones across the regions identified by linkage analysis to harbor the disease genes. CA repeats will be developed from YAC clones at 1 Mb intervals and used to identify by linkage analysis those YAC clones flanking the disease loci. cDNA selection and exon trapping will be applied to directly identify coding regions from those genomic clones identified in the smallest region harboring the genes. Resulting cDNA clones will be sequenced to test for criteria of coding regions. Candidate cDNA and corresponding genomic clones will be used to examine affected patients for mutations by single strand conformational polymorphisms (SSCP) and denaturing gradient gel electrophoresis (DOGE). The molecular and genetic abnormality for each disorder will be described by cloning and characterizing the genes responsible for these sight disorders. Eventual sequencing of the genes will allow a determination of the protein structure coded by the gene and its physiologic function. This knowledge will allow new insights into several common sight disorders.
| Project Number : | 5R01EY010514-02 |
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| ICD : | NATIONAL EYE INSTITUTE |
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| IRG : | VISC |
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| Project Terms : | eye disorder, genetic disorder, linkage mapping, molecular cloning, retina disorder congenital eye disorder human genetic material tag, yeast artificial chromosome |
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CLONING RETINAL GENES LOCATED ON CHROMOSOME 11
(1997)
Abstract :
Genes coding for inherited eye disorders have been mapped by family studies and genetic linkage tests to two specific regions (11 q13 and 11p14/15.1) on human chromosome 11. The aim of this proposal is to locate and clone these genes associated with impaired sight. This will be accomplished by generating an ordered overlapping clone map consisting of chromosome ii specific YAC (yeast artificial chromosome) clones across the regions identified by linkage analysis to harbor the disease genes. CA repeats will be developed from YAC clones at 1 Mb intervals and used to identify by linkage analysis those YAC clones flanking the disease loci. cDNA selection and exon trapping will be applied to directly identify coding regions from those genomic clones identified in the smallest region harboring the genes. Resulting cDNA clones will be sequenced to test for criteria of coding regions. Candidate cDNA and corresponding genomic clones will be used to examine affected patients for mutations by single strand conformational polymorphisms (SSCP) and denaturing gradient gel electrophoresis (DOGE). The molecular and genetic abnormality for each disorder will be described by cloning and characterizing the genes responsible for these sight disorders. Eventual sequencing of the genes will allow a determination of the protein structure coded by the gene and its physiologic function. This knowledge will allow new insights into several common sight disorders.
| Project Number : | 1R01EY010514-01 |
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| ICD : | NATIONAL EYE INSTITUTE |
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| IRG : | VISC |
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| Project Terms : | eye disorder, genetic disorder, linkage mapping, molecular cloning, retina disorder congenital eye disorder human genetic material tag, yeast artificial chromosome |
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MAPPING HUMAN GENES AND ASSOCIATED DISEASES
(1997)
Abstract :
The long range goal of this proposal continues to be the mapping of human genes (functional loci) to specific chromosomes, regions of chromosomes and high resolution gene maps. The genes we have chosen to map play a significant role in human health and development. For this application, we have identified over 1,100 genes with sequences in databases that have not been mapped within the human genome. We will develop STSs from these sequences and map them to specific chromosomes and regions of chromosomes using our well-characterized and successful cell hybrid panels. After these gene markers have been mapped, primers will be sent to the MIT Center for Genome Research and the Iowa Cooperative Human Linkage Center for incorporation with their physical and gene linkage maps, respectively. An additional goal will be to continue mapping 75-100 human genes/year associated with disease and notable biological features that are requested by our collaborators. These genes will also be candidates for generating STSs from their sequences and incorporating them into the developing physical and linkage maps. The significance of this proposal is that (1) large numbers of human genes necessary for normal human biology will be mapped, (2) human gene sequences will be located in the genome at a specific site, (3) this number of mapped human genes will increase the resolution and completeness of the MIT and Iowa Center maps by about 10%, (4) these gene markers will add a significant biological feature to the developing physical and linkage maps that are being constructed with random genome markers, and (5) these additional mapped gene markers will help characterize, diagnose and predict genetic disease.
| Project Number : | 5R01HG000333-23 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | GNM |
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| Project Terms : | developmental genetics, genetic disorder, genetic mapping, genetic marker, linkage mapping, neoplasm /cancer genetics, oncogene chromosome translocation, cytogenetics, gene expression, gene rearrangement, genetic library, genetic model, genetic regulation, nucleic acid sequence, sequence tagged site human genetic material tag, human tissue, in situ hybridization, molecular cloning, northern blotting, nucleic acid probe, polymerase chain reaction, southern blotting |
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MAPPING HUMAN GENES AND ASSOCIATED DISEASES
(1997)
Abstract :
The long range goal of this proposal continues to be the mapping of human genes (functional loci) to specific chromosomes, regions of chromosomes and high resolution gene maps. The genes we have chosen to map play a significant role in human health and development. For this application, we have identified over 1,100 genes with sequences in databases that have not been mapped within the human genome. We will develop STSs from these sequences and map them to specific chromosomes and regions of chromosomes using our well-characterized and successful cell hybrid panels. After these gene markers have been mapped, primers will be sent to the MIT Center for Genome Research and the Iowa Cooperative Human Linkage Center for incorporation with their physical and gene linkage maps, respectively. An additional goal will be to continue mapping 75-100 human genes/year associated with disease and notable biological features that are requested by our collaborators. These genes will also be candidates for generating STSs from their sequences and incorporating them into the developing physical and linkage maps. The significance of this proposal is that (1) large numbers of human genes necessary for normal human biology will be mapped, (2) human gene sequences will be located in the genome at a specific site, (3) this number of mapped human genes will increase the resolution and completeness of the MIT and Iowa Center maps by about 10%, (4) these gene markers will add a significant biological feature to the developing physical and linkage maps that are being constructed with random genome markers, and (5) these additional mapped gene markers will help characterize, diagnose and predict genetic disease.
| Project Number : | 2R01HG000333-22 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | GNM |
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| Project Terms : | developmental genetics, genetic disorder, genetic mapping, genetic marker, linkage mapping, neoplasm /cancer genetics, oncogene chromosome translocation, cytogenetics, gene expression, gene rearrangement, genetic library, genetic model, genetic regulation, nucleic acid sequence, sequence tagged site human genetic material tag, human tissue, in situ hybridization, molecular cloning, northern blotting, nucleic acid probe, polymerase chain reaction, southern blotting |
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CLONING CHROMOSOME 11 GENES INVOLVED IN NEOPLASIA
(1997)
Abstract :
Research is proposed to identify, clone and characterize potential tumor or growth suppressor genes that, through inactivation, contribute to the development of a large variety of cancers, including those exhibiting increased prevalence in Beckwith- Wiedemann Syndrome (BWS). The chromosome 11p15.5 interval between the anonymous DNA marker D11S12 and the insulin-like growth factor 2 (IGF2) gene is implicated in tumor suppression and BWS. We have mapped into this region two chromosome rearrangements (one from a rhabdoid tumor and the other associated with BWS) that may disrupt and therefore pinpoint a growth or tumor suppressor gene(s). Long- range restriction mapping indicates that there is little more than 2200 kb separating D11S12 and IGF2, a genomic length easily amenable to cloning in overlapping YACs. Using a battery of 37 probes (one probe per 60 kb) cognate YACs will be isolated from a 4-fold chromosome 11 YAC library and contigs assembled by probe content analysis and walking using YAC-derived Alu-PCR products. A significant advantage of using this YAC library for a walking approach is the rare incidence of human-human chimeric clones (<1%). YAC clones found to map in the chromosome rearrangement breakpoint region will be used to analyze metaphase chromosomes containing the rearrangements by fluorescence in situ hybridization (FISH). Those YACs found to "cross" the breakpoints will be used to isolate corresponding cosmid clones which will then be screened by exon amplification for the presence of gene coding sequences. These exons will then be used to isolate cDNAs. Alternatively, YACs that span breakpoints or corresponding cosmids will be used to identify encoded genes by a cDNA selection technique. Mutation assays for candidate genes will be used to analyze tumors and additional BWS patients. The cloning and characterization of putative growth or tumor suppressor genes in this chromosome region will help address questions pertaining to the number and type of genes involved in the wide spectrum of tumors showing loss of heterozygosity (LOH) in this genomic segment. Furthermore, molecular assays of both diagnostic and prognostic value may be developed once genes contributing to tumorigenesis are characterized.
| Project Number : | 1R01CA063333-01 |
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| ICD : | NATIONAL CANCER INSTITUTE |
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| IRG : | MGN |
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| Project Terms : | growth factor, molecular cloning, molecular oncology, neoplasm /cancer genetics, restriction mapping, tumor suppressor gene complementary DNA, gene rearrangement, genetic marker, loss of heterozygosity, nucleic acid sequence, restriction fragment length polymorphism human genetic material tag, human tissue, in situ hybridization, nucleic acid probe, polymerase chain reaction, pulsed field gel electrophoresis, southern blotting, transfection, yeast artificial chromosome |
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CLONING CHROMOSOME 11 GENES INVOLVED IN NEOPLASIA
(1997)
Abstract :
Research is proposed to identify, clone and characterize potential tumor or growth suppressor genes that, through inactivation, contribute to the development of a large variety of cancers, including those exhibiting increased prevalence in Beckwith- Wiedemann Syndrome (BWS). The chromosome 11p15.5 interval between the anonymous DNA marker D11S12 and the insulin-like growth factor 2 (IGF2) gene is implicated in tumor suppression and BWS. We have mapped into this region two chromosome rearrangements (one from a rhabdoid tumor and the other associated with BWS) that may disrupt and therefore pinpoint a growth or tumor suppressor gene(s). Long- range restriction mapping indicates that there is little more than 2200 kb separating D11S12 and IGF2, a genomic length easily amenable to cloning in overlapping YACs. Using a battery of 37 probes (one probe per 60 kb) cognate YACs will be isolated from a 4-fold chromosome 11 YAC library and contigs assembled by probe content analysis and walking using YAC-derived Alu-PCR products. A significant advantage of using this YAC library for a walking approach is the rare incidence of human-human chimeric clones (<1%). YAC clones found to map in the chromosome rearrangement breakpoint region will be used to analyze metaphase chromosomes containing the rearrangements by fluorescence in situ hybridization (FISH). Those YACs found to "cross" the breakpoints will be used to isolate corresponding cosmid clones which will then be screened by exon amplification for the presence of gene coding sequences. These exons will then be used to isolate cDNAs. Alternatively, YACs that span breakpoints or corresponding cosmids will be used to identify encoded genes by a cDNA selection technique. Mutation assays for candidate genes will be used to analyze tumors and additional BWS patients. The cloning and characterization of putative growth or tumor suppressor genes in this chromosome region will help address questions pertaining to the number and type of genes involved in the wide spectrum of tumors showing loss of heterozygosity (LOH) in this genomic segment. Furthermore, molecular assays of both diagnostic and prognostic value may be developed once genes contributing to tumorigenesis are characterized.
| Project Number : | 5R01CA063333-02 |
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| ICD : | NATIONAL CANCER INSTITUTE |
|---|
| IRG : | MGN |
|---|
| Project Terms : | growth factor, molecular cloning, molecular oncology, neoplasm /cancer genetics, restriction mapping, tumor suppressor gene complementary DNA, gene rearrangement, genetic marker, loss of heterozygosity, nucleic acid sequence, restriction fragment length polymorphism human genetic material tag, human tissue, in situ hybridization, nucleic acid probe, polymerase chain reaction, pulsed field gel electrophoresis, southern blotting, transfection, yeast artificial chromosome |
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FIFTH INTERNATIONAL CHROMOSOME 11 WORKSHOP
(1997)
| Project Number : | 1R13HG001457-01 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | GRRC |
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MAPPING HUMAN CHROMOSOME 11
(1996)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 3R01HG000359-05S1 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | SRC |
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MAPPING HUMAN CHROMOSOME 11
(1996)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 5R01HG000359-05 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | SRC |
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| Project Terms : | chromosome, genetic mapping, molecular cloning chromosome deletion, chromosome translocation, cytogenetics, endonuclease, genetic library, genetic manipulation, genetic marker, hybrid cell, linkage mapping, molecular pathology, nucleic acid sequence gel electrophoresis, hamster, human genetic material tag, human tissue, nucleic acid probe, pulsed field gel electrophoresis |
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MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1994)
Abstract :
There is an acute shortage of human functional loci mapped to specific chromosomal sites. Fewer than 1700 mapped genes (~3% of the total genome) are available to address basic genetic questions regarding the numbers and organization of genes, gene regulation, genetic mechanisms, and disease. The goal for this research continues to be the description of the human gene map, its association with disease, and its contribution to understanding genetic principles. Specific aims for this period are three- fold: (1) generate detailed gene maps for three subregions of chromosome 11 associated with neoplasia and developmental disorders; (2) advance the gene map of all chromosomes; and (3) characterize mapped genetic disease. Several methodologies are proposed to isolate coding sequences from the WAGR 11p13 subregion, the PTH-pter subregion of p15.5, and the CD3-ETS1 subregion of q23.3. These regions have the potential to yield necessary information concerning genetic mechanisms and principles because of their location on chromosome 11 and the array of disorders associated with them. The description of the gene map for these three regions, with spatial and temporal expression profiles for genes, will enable us to address fundamental questions concerning gene number, the density of genes at the subtelomeric vs. more proximal locations, the relationship of CpG islands and genes, genome organization and gene regulation, and genomic imprinting. Candidate genes will be used to characterize the several disorders and chromosomal abnormalities mapped to these subregions, such as defining the number and type of genes involved in a contiguous gene syndrome, and the identification of genes disrupted or activated at translocation breakpoints or inactivated by other genetic mechanisms. Addressing these aspects for all chromosomes, we propose to advance all functional maps. These studies will map genes for genetic disease, neoplasia and those with defined biological function. These studies will allow us to correlate basic functions, disease, and genetic phenomena with map location.
| Project Number : | 2R01HG000333-19 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | GNM |
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| Project Terms : | chromosome disorder, developmental genetics, genetic disorder, genetic mapping, genetic marker, linkage mapping, neoplasm /cancer genetics, oncogene chromosome aberration, chromosome translocation, cytogenetics, gene expression, gene rearrangement, genetic model, genetic regulation, genomic library, molecular genetics, nucleic acid sequence, telomere endonuclease, gel electrophoresis, human genetic material tag, human tissue from nonrelated source, in situ hybridization, molecular cloning, northern blotting, nucleic acid probe, polymerase chain reaction, radiotracer, southern blotting |
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MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1994)
Abstract :
There is an acute shortage of human functional loci mapped to specific chromosomal sites. Fewer than 1700 mapped genes (~3% of the total genome) are available to address basic genetic questions regarding the numbers and organization of genes, gene regulation, genetic mechanisms, and disease. The goal for this research continues to be the description of the human gene map, its association with disease, and its contribution to understanding genetic principles. Specific aims for this period are three- fold: (1) generate detailed gene maps for three subregions of chromosome 11 associated with neoplasia and developmental disorders; (2) advance the gene map of all chromosomes; and (3) characterize mapped genetic disease. Several methodologies are proposed to isolate coding sequences from the WAGR 11p13 subregion, the PTH-pter subregion of p15.5, and the CD3-ETS1 subregion of q23.3. These regions have the potential to yield necessary information concerning genetic mechanisms and principles because of their location on chromosome 11 and the array of disorders associated with them. The description of the gene map for these three regions, with spatial and temporal expression profiles for genes, will enable us to address fundamental questions concerning gene number, the density of genes at the subtelomeric vs. more proximal locations, the relationship of CpG islands and genes, genome organization and gene regulation, and genomic imprinting. Candidate genes will be used to characterize the several disorders and chromosomal abnormalities mapped to these subregions, such as defining the number and type of genes involved in a contiguous gene syndrome, and the identification of genes disrupted or activated at translocation breakpoints or inactivated by other genetic mechanisms. Addressing these aspects for all chromosomes, we propose to advance all functional maps. These studies will map genes for genetic disease, neoplasia and those with defined biological function. These studies will allow us to correlate basic functions, disease, and genetic phenomena with map location.
| Project Number : | 5R01HG000333-20 |
|---|
| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
|---|
| IRG : | GNM |
|---|
| Project Terms : | chromosome disorder, developmental genetics, genetic disorder, genetic mapping, genetic marker, linkage mapping, neoplasm /cancer genetics, oncogene chromosome aberration, chromosome translocation, cytogenetics, gene expression, gene rearrangement, genetic library, genetic model, genetic regulation, molecular genetics, nucleic acid sequence, telomere endonuclease, gel electrophoresis, human genetic material tag, human tissue, in situ hybridization, molecular cloning, northern blotting, nucleic acid probe, polymerase chain reaction, radiotracer, southern blotting |
|---|
MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1994)
Abstract :
There is an acute shortage of human functional loci mapped to specific chromosomal sites. Fewer than 1700 mapped genes (~3% of the total genome) are available to address basic genetic questions regarding the numbers and organization of genes, gene regulation, genetic mechanisms, and disease. The goal for this research continues to be the description of the human gene map, its association with disease, and its contribution to understanding genetic principles. Specific aims for this period are three- fold: (1) generate detailed gene maps for three subregions of chromosome 11 associated with neoplasia and developmental disorders; (2) advance the gene map of all chromosomes; and (3) characterize mapped genetic disease. Several methodologies are proposed to isolate coding sequences from the WAGR 11p13 subregion, the PTH-pter subregion of p15.5, and the CD3-ETS1 subregion of q23.3. These regions have the potential to yield necessary information concerning genetic mechanisms and principles because of their location on chromosome 11 and the array of disorders associated with them. The description of the gene map for these three regions, with spatial and temporal expression profiles for genes, will enable us to address fundamental questions concerning gene number, the density of genes at the subtelomeric vs. more proximal locations, the relationship of CpG islands and genes, genome organization and gene regulation, and genomic imprinting. Candidate genes will be used to characterize the several disorders and chromosomal abnormalities mapped to these subregions, such as defining the number and type of genes involved in a contiguous gene syndrome, and the identification of genes disrupted or activated at translocation breakpoints or inactivated by other genetic mechanisms. Addressing these aspects for all chromosomes, we propose to advance all functional maps. These studies will map genes for genetic disease, neoplasia and those with defined biological function. These studies will allow us to correlate basic functions, disease, and genetic phenomena with map location.
| Project Number : | 5R01HG000333-21 |
|---|
| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
|---|
| IRG : | GNM |
|---|
| Project Terms : | chromosome disorder, developmental genetics, genetic disorder, genetic mapping, genetic marker, linkage mapping, neoplasm /cancer genetics, oncogene chromosome aberration, chromosome translocation, cytogenetics, gene expression, gene rearrangement, genetic library, genetic model, genetic regulation, genomic imprinting, molecular genetics, nucleic acid sequence, telomere endonuclease, gel electrophoresis, human genetic material tag, human tissue, in situ hybridization, molecular cloning, northern blotting, nucleic acid probe, polymerase chain reaction, radiotracer, southern blotting |
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GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE
(1994)
Abstract :
Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.
| Project Number : | 5R01HD005196-21 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | arylsulfatase, developmental genetics, enzyme biosynthesis, gene expression, glucuronosyltransferase, human population genetics, inborn lysosomal enzyme disorder RNA biosynthesis, Sandhoff Jatzkewitz disease, Tay Sachs disease, antepartum diagnosis, beta N acetylhexosaminidase, cell transformation, ceramide trihexosidosis, chromosome aberration, enzyme mechanism, gangliosidosis GM1, gene complementation, gene mutation, genetic counseling, genetic disorder diagnosis, genetic marker, genotype, heterozygote, inborn metabolism disorder diagnosis, isozyme, linkage mapping, lipomucopolysaccharidosis, metachromatic leukoencephalopathy, sialidase Golgi apparatus, chromosome translocation, clone cell, fibroblast, gel electrophoresis, human clinical subject, immunofluorescence technique, laboratory mouse, laboratory rabbit, molecular cloning, nucleic acid hybridization, nucleic acid probe |
|---|
MAPPING HUMAN CHROMOSOME 11
(1993)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 5R01GM040876-02 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | SRC |
|---|
| Project Terms : | GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, genetic mapping CELL HYBRIDS, DISEASES, MOLECULAR LEVEL STUDIES, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, CYTOGENETICS, GENETICS, GENETIC LIBRARIES, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, CHROMOSOME MUTATION, DELETION, NUCLEASES, ENDONUCLEASES, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, genetic manipulation ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL |
|---|
MAPPING HUMAN CHROMOSOME 11
(1993)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 1R01GM040876-01 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | SRC |
|---|
| Project Terms : | GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, genetic mapping CELL HYBRIDS, DISEASES, MOLECULAR LEVEL STUDIES, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, CYTOGENETICS, GENETICS, GENETIC LIBRARIES, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, CHROMOSOME MUTATION, DELETION, NUCLEASES, ENDONUCLEASES, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, genetic manipulation ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL |
|---|
MAPPING HUMAN CHROMOSOME 11
(1993)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 5R01HG000359-04 |
|---|
| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
|---|
| IRG : | SRC |
|---|
| Project Terms : | chromosome, genetic mapping, molecular cloning chromosome deletion, chromosome translocation, cytogenetics, endonuclease, genetic manipulation, genetic marker, genomic library, hybrid cell, linkage mapping, molecular pathology, nucleic acid sequence gel electrophoresis, hamster, human genetic material tag, human tissue from nonrelated source, nucleic acid probe, pulsed field gel electrophoresis |
|---|
MAPPING HUMAN CHROMOSOME 11
(1993)
Abstract :
A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.
| Project Number : | 8R01HG000359-03 |
|---|
| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
|---|
| IRG : | SRC |
|---|
| Project Terms : | GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, genetic mapping CELL HYBRIDS, DISEASES, MOLECULAR LEVEL STUDIES, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, CYTOGENETICS, GENETICS, GENETIC LIBRARIES, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, CHROMOSOME MUTATION, DELETION, NUCLEASES, ENDONUCLEASES, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, genetic manipulation ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL |
|---|
GENETICS OF HUMAN DEVELOPMENT & METABOLIC DISEASE
(1993)
Abstract :
Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.
| Project Number : | 2R01HD005196-17A1 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL COMPONENTS, LYSOSOMES, DISEASES, MOLECULAR LEVEL STUDIES, ENZYMES BIOSYNTHESIS, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, POPULATION GENETICS HUMAN, GLYCOSYLTRANSFERASES, GLUCURONOSYLTRANSFERASES, SULFATASES, ARYLSULFATASES, TRANSFERASES, genetic mapping AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-FUCOSIDASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CARBOHYDRASES, NEURAMINIDASE, CELL HYBRIDS, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, STRUCTURAL GENES, GENETICS, GENETIC REGULATION, TRANSCRIPTION, GENETICS, GENOTYPES, GENETICS, GENOTYPES, HETEROZYGOTES, GENETICS, MUTATION, CHROMOSOME MUTATION, GENETICS, MUTATION, GENE MUTATION, GENETICS, MUTATION, MUTANTS, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, ISOMERASES, MANNOSEPHOSPHATE ISOMERASE, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEIC ACIDS METABOLISM, NUCLEIC ACIDS SYNTHESIS, RNA, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, PROTEIN (PEPTIDE) SEQUENCE, genetic manipulation, protein biosynthesis ANIMALS, CHORDATES, MAMMALS, LAGOMORPHS, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), CELL COMPONENTS, GOLGI APPARATUS, CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, nucleic acid hybridization |
|---|
GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE
(1993)
Abstract :
Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.
| Project Number : | 5R01HD005196-18 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL COMPONENTS, LYSOSOMES, DISEASES, MOLECULAR LEVEL STUDIES, ENZYMES BIOSYNTHESIS, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, POPULATION GENETICS HUMAN, GLYCOSYLTRANSFERASES, GLUCURONOSYLTRANSFERASES, SULFATASES, ARYLSULFATASES, TRANSFERASES, genetic mapping AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-FUCOSIDASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CARBOHYDRASES, NEURAMINIDASE, CELL HYBRIDS, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, STRUCTURAL GENES, GENETICS, GENETIC REGULATION, TRANSCRIPTION, GENETICS, GENOTYPES, GENETICS, GENOTYPES, HETEROZYGOTES, GENETICS, MUTATION, CHROMOSOME MUTATION, GENETICS, MUTATION, GENE MUTATION, GENETICS, MUTATION, MUTANTS, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, ISOMERASES, MANNOSEPHOSPHATE ISOMERASE, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEIC ACIDS METABOLISM, NUCLEIC ACIDS SYNTHESIS, RNA, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, PROTEIN (PEPTIDE) SEQUENCE, genetic manipulation, protein biosynthesis ANIMALS, CHORDATES, MAMMALS, LAGOMORPHS, ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), CELL COMPONENTS, GOLGI APPARATUS, CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, nucleic acid hybridization |
|---|
GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE
(1993)
Abstract :
Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.
| Project Number : | 5R01HD005196-19 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL COMPONENTS, LYSOSOMES, DISEASES, MOLECULAR LEVEL STUDIES, ENZYMES BIOSYNTHESIS, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, POPULATION GENETICS HUMAN, GLYCOSYLTRANSFERASES, GLUCURONOSYLTRANSFERASES, SULFATASES, ARYLSULFATASES, TRANSFERASES, genetic mapping AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-FUCOSIDASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CARBOHYDRASES, NEURAMINIDASE, CELL HYBRIDS, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, GENETIC MARKERS, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, STRUCTURAL GENES, GENETICS, GENETIC REGULATION, TRANSCRIPTION, GENETICS, GENOTYPES, GENETICS, GENOTYPES, HETEROZYGOTES, GENETICS, MUTATION, CHROMOSOME MUTATION, GENETICS, MUTATION, GENE MUTATION, GENETICS, MUTATION, MUTANTS, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, ISOMERASES, MANNOSEPHOSPHATE ISOMERASE, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEIC ACIDS BIOSYNTHESIS, RNA BIOSYNTHESIS, NUCLEIC ACIDS METABOLISM, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, PROTEIN (PEPTIDE) SEQUENCE, genetic manipulation, protein biosynthesis ANIMALS, CHORDATES, MAMMALS, LAGOMORPHS, RABBITS (LABORATORY), ANIMALS, CHORDATES, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), CELL COMPONENTS, GOLGI APPARATUS, CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, NUCLEIC ACIDS, NUCLEIC ACID PROBES, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, nucleic acid hybridization |
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GENETICS OF HUMAN DEVELOPMENT AND METABOLIC DISEASE
(1993)
Abstract :
Human development is the summation of individual biochemical processes, each genetically programed to function in a systematic way, leading to the final expression and localization of an enzyme or protein. The development and localization of an enzyme require several genes which function as processing, temporal, architectural, targeting and receptor genes acting on a structural gene product. Inherited lysosomal enzyme disorders associated with abnormal development provided excellent models for studying the different numbers and types of genes required for the development of an enzyme. This study is designed to dissect, identify and characterize several new genes necessary for the final realization of a lysosomal enzyme. To accomplish this, 2 sets of lysosomal enzyme disorders will be studied: the mucolipidoses and the arylsulfatase A deficiency disorders. Each involve several affected gene all of which are required for the development of a lysosomal enzyme. The mucolipidoses (ML) consist of MLII and MLIII characterized by the golgi GlcNAc-P- transferase (GNPT) deficiency affecting the biosynthesis and localization of lysosomal enzymes. We have identified at least 3 genes that are required. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Our evidence suggests at least 10 genes involved in the final expression of arylsulfatase-A (ARSA). Therefore, this study has the potential of dissecting and identifying at least 10 new genes involved in the processing, targeting and development of lysosomal enzymes, in general, and ARSA, in particular. Somatic cell studies will genetically dissect and identify the genes. Genetic, biochemical, immunological, and molecular studies are proposed to characterize the genes and enzymes. Large families have been identified for mucolipidosis gene linkage studies. Our evidence indicates several types of genes, including structural, processing, targeting, temporal and receptor. Cloned genes will be used to characterize GNPT organization, disease- associated mutants, and gene expression. All markers developed will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe involved in the expression, processing, and targeting of lysosomal enzymes, which will contribute basic information for human development and genetics and the biosynthesis of the lysosome.
| Project Number : | 5R01HD005196-20 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | MGN |
|---|
| Project Terms : | arylsulfatase, developmental genetics, enzyme biosynthesis, gene expression, genetic mapping, glucuronosyltransferase, human population genetics, lysosome, molecular pathology, transferase RNA biosynthesis, Sandhoff Jatzkewitz disease, Tay Sachs disease, acid phosphatase, adenosine deaminase, alpha L fucosidase, alpha galactosidase, antepartum diagnosis, beta N acetylhexosaminidase, beta glucuronidase, ceramide trihexosidosis, chromatin, chromosome aberration, enzyme mechanism, gangliosidosis GM1, gene complementation, gene mutation, genetic code, genetic counseling, genetic disorder diagnosis, genetic manipulation, genetic marker, genetic transcription, genotype, heterozygote, hybrid cell, immunodeficiency, immunoglobulin, inborn metabolism disorder diagnosis, isozyme, linkage mapping, lipomucopolysaccharidosis, mannose 6 phosphate isomerase, metachromatic leukoencephalopathy, mutant, nucleic acid metabolism, protein biosynthesis, protein sequence, sialidase, somatic cell transformation, structural gene Golgi apparatus, chromosome translocation, clone cell, fibroblast, gel electrophoresis, immunofluorescence technique, laboratory mouse, laboratory rabbit, molecular cloning, nucleic acid hybridization, nucleic acid probe |
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MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1991)
Abstract :
Molecular and somatic cell genetic research is proposed to continue extensive gene mapping studies for characterizing the physical and genetic maps of the human. We will concentrate on understanding the chromosomal location and organization of growth control genes and the extent of their involvement and that of DNA segments in chromosomal rearrangements associated with cancer. The markers for mapping on human chromosomes include large numbers of (1) genes associated with metabolic disease and fatal disorders, (2) DNA segments assigned to highly specific chromosomal regions associated with Wilms' tumor (chromosome 11p13 deletion), small cell carcinoma of the lung (chromosome 3p14-23 deletion), Down's syndrome (chromosome 21q22), and breakpoints associated with non-random chromosomal rearrangement observed in specific cancers (11q13, 11q23, 3p13, 3p14, 3p21, 21q22), (3) genes associated with transformation that are induced in human cells by growth factors, epidermal growth factor and transforming growth factor-Alpha, which compete for the same receptor--the cellular homolog of the oncogene v-erb B, and (5) genes whose transcription is enhanced in leukemic cells. The gene markers will be chromosomally assigned by specific site in situ mapping and chromosome and regional mapping panels of somatic cell hybrids. DNA probes that map at a chromosome breakpoint or in a deletion associated with cancer will be characterized to determine sequences at break sites and adjacent probes to study these regions will be isolated by chromosome walking. All gene probes studied will be utilized to identify DNA polymorphisms (RFLPs) for linkage relationships, linear organization of the genome, and genetic counseling. The inherited nature of these DNA polymorphisms will be determined in 3 generation families. Genes associated with inherited disorders, abnormal growth and cancer will be mapped in the mouse using mouse-Chinese hamster cell hybrids to determine and predict human disease, evolution and chromosome assignment. Studies will be conducted to generate human-mouse cell hybrids that retain a single human chromosome for rapid gene mapping purposes. This research is designed to locate human genes associated with molecular disease and cancer to specific chromosomal sites for genetically understanding human disease, gene organization and control, and for genetic diagnosis and counseling.
| Project Number : | 2R01GM020454-14 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA |
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MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1991)
Abstract :
Molecular and somatic cell genetic research is proposed to continue extensive gene mapping studies for characterizing the physical and genetic maps of the human. We will concentrate on understanding the chromosomal location and organization of growth control genes and the extent of their involvement and that of DNA segments in chromosomal rearrangements associated with cancer. The markers for mapping on human chromosomes include large numbers of (1) genes associated with metabolic disease and fatal disorders, (2) DNA segments assigned to highly specific chromosomal regions associated with Wilms' tumor (chromosome 11p13 deletion), small cell carcinoma of the lung (chromosome 3p14-23 deletion), Down's syndrome (chromosome 21q22), and breakpoints associated with non-random chromosomal rearrangement observed in specific cancers (11q13, 11q23, 3p13, 3p14, 3p21, 21q22), (3) genes associated with transformation that are induced in human cells by growth factors, epidermal growth factor and transforming growth factor-Alpha, which compete for the same receptor--the cellular homolog of the oncogene v-erb B, and (5) genes whose transcription is enhanced in leukemic cells. The gene markers will be chromosomally assigned by specific site in situ mapping and chromosome and regional mapping panels of somatic cell hybrids. DNA probes that map at a chromosome breakpoint or in a deletion associated with cancer will be characterized to determine sequences at break sites and adjacent probes to study these regions will be isolated by chromosome walking. All gene probes studied will be utilized to identify DNA polymorphisms (RFLPs) for linkage relationships, linear organization of the genome, and genetic counseling. The inherited nature of these DNA polymorphisms will be determined in 3 generation families. Genes associated with inherited disorders, abnormal growth and cancer will be mapped in the mouse using mouse-Chinese hamster cell hybrids to determine and predict human disease, evolution and chromosome assignment. Studies will be conducted to generate human-mouse cell hybrids that retain a single human chromosome for rapid gene mapping purposes. This research is designed to locate human genes associated with molecular disease and cancer to specific chromosomal sites for genetically understanding human disease, gene organization and control, and for genetic diagnosis and counseling.
| Project Number : | 8R01HG000333-18 |
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| ICD : | NATIONAL HUMAN GENOME RESEARCH INSTITUTE |
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| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, NUCLEIC ACIDS BIOSYNTHESIS, DNA BIOSYNTHESIS, NUCLEIC ACIDS BIOSYNTHESIS, RNA BIOSYNTHESIS, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS, RRNA, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), cell fusion, genetic manipulation, protein biosynthesis BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, GENETIC MAPPING, CHROMOSOME WALKING, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA |
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MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1991)
Abstract :
Molecular and somatic cell genetic research is proposed to continue extensive gene mapping studies for characterizing the physical and genetic maps of the human. We will concentrate on understanding the chromosomal location and organization of growth control genes and the extent of their involvement and that of DNA segments in chromosomal rearrangements associated with cancer. The markers for mapping on human chromosomes include large numbers of (1) genes associated with metabolic disease and fatal disorders, (2) DNA segments assigned to highly specific chromosomal regions associated with Wilms' tumor (chromosome 11p13 deletion), small cell carcinoma of the lung (chromosome 3p14-23 deletion), Down's syndrome (chromosome 21q22), and breakpoints associated with non-random chromosomal rearrangement observed in specific cancers (11q13, 11q23, 3p13, 3p14, 3p21, 21q22), (3) genes associated with transformation that are induced in human cells by growth factors, epidermal growth factor and transforming growth factor-Alpha, which compete for the same receptor--the cellular homolog of the oncogene v-erb B, and (5) genes whose transcription is enhanced in leukemic cells. The gene markers will be chromosomally assigned by specific site in situ mapping and chromosome and regional mapping panels of somatic cell hybrids. DNA probes that map at a chromosome breakpoint or in a deletion associated with cancer will be characterized to determine sequences at break sites and adjacent probes to study these regions will be isolated by chromosome walking. All gene probes studied will be utilized to identify DNA polymorphisms (RFLPs) for linkage relationships, linear organization of the genome, and genetic counseling. The inherited nature of these DNA polymorphisms will be determined in 3 generation families. Genes associated with inherited disorders, abnormal growth and cancer will be mapped in the mouse using mouse-Chinese hamster cell hybrids to determine and predict human disease, evolution and chromosome assignment. Studies will be conducted to generate human-mouse cell hybrids that retain a single human chromosome for rapid gene mapping purposes. This research is designed to locate human genes associated with molecular disease and cancer to specific chromosomal sites for genetically understanding human disease, gene organization and control, and for genetic diagnosis and counseling.
| Project Number : | 5R01GM020454-17 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, RRNA, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), cell fusion, genetic manipulation, protein biosynthesis BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA |
|---|
MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1991)
Abstract :
Molecular and somatic cell genetic research is proposed to continue extensive gene mapping studies for characterizing the physical and genetic maps of the human. We will concentrate on understanding the chromosomal location and organization of growth control genes and the extent of their involvement and that of DNA segments in chromosomal rearrangements associated with cancer. The markers for mapping on human chromosomes include large numbers of (1) genes associated with metabolic disease and fatal disorders, (2) DNA segments assigned to highly specific chromosomal regions associated with Wilms' tumor (chromosome 11p13 deletion), small cell carcinoma of the lung (chromosome 3p14-23 deletion), Down's syndrome (chromosome 21q22), and breakpoints associated with non-random chromosomal rearrangement observed in specific cancers (11q13, 11q23, 3p13, 3p14, 3p21, 21q22), (3) genes associated with transformation that are induced in human cells by growth factors, epidermal growth factor and transforming growth factor-Alpha, which compete for the same receptor--the cellular homolog of the oncogene v-erb B, and (5) genes whose transcription is enhanced in leukemic cells. The gene markers will be chromosomally assigned by specific site in situ mapping and chromosome and regional mapping panels of somatic cell hybrids. DNA probes that map at a chromosome breakpoint or in a deletion associated with cancer will be characterized to determine sequences at break sites and adjacent probes to study these regions will be isolated by chromosome walking. All gene probes studied will be utilized to identify DNA polymorphisms (RFLPs) for linkage relationships, linear organization of the genome, and genetic counseling. The inherited nature of these DNA polymorphisms will be determined in 3 generation families. Genes associated with inherited disorders, abnormal growth and cancer will be mapped in the mouse using mouse-Chinese hamster cell hybrids to determine and predict human disease, evolution and chromosome assignment. Studies will be conducted to generate human-mouse cell hybrids that retain a single human chromosome for rapid gene mapping purposes. This research is designed to locate human genes associated with molecular disease and cancer to specific chromosomal sites for genetically understanding human disease, gene organization and control, and for genetic diagnosis and counseling.
| Project Number : | 5R01GM020454-16 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, RRNA, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), cell fusion, genetic manipulation, protein biosynthesis BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, HUMAN TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PR OJECT, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA |
|---|
MAPPING MOLECULAR DISEASE AND CANCER-RELATED GENES
(1991)
Abstract :
Molecular and somatic cell genetic research is proposed to continue extensive gene mapping studies for characterizing the physical and genetic maps of the human. We will concentrate on understanding the chromosomal location and organization of growth control genes and the extent of their involvement and that of DNA segments in chromosomal rearrangements associated with cancer. The markers for mapping on human chromosomes include large numbers of (1) genes associated with metabolic disease and fatal disorders, (2) DNA segments assigned to highly specific chromosomal regions associated with Wilms' tumor (chromosome 11p13 deletion), small cell carcinoma of the lung (chromosome 3p14-23 deletion), Down's syndrome (chromosome 21q22), and breakpoints associated with non-random chromosomal rearrangement observed in specific cancers (11q13, 11q23, 3p13, 3p14, 3p21, 21q22), (3) genes associated with transformation that are induced in human cells by growth factors, epidermal growth factor and transforming growth factor-Alpha, which compete for the same receptor--the cellular homolog of the oncogene v-erb B, and (5) genes whose transcription is enhanced in leukemic cells. The gene markers will be chromosomally assigned by specific site in situ mapping and chromosome and regional mapping panels of somatic cell hybrids. DNA probes that map at a chromosome breakpoint or in a deletion associated with cancer will be characterized to determine sequences at break sites and adjacent probes to study these regions will be isolated by chromosome walking. All gene probes studied will be utilized to identify DNA polymorphisms (RFLPs) for linkage relationships, linear organization of the genome, and genetic counseling. The inherited nature of these DNA polymorphisms will be determined in 3 generation families. Genes associated with inherited disorders, abnormal growth and cancer will be mapped in the mouse using mouse-Chinese hamster cell hybrids to determine and predict human disease, evolution and chromosome assignment. Studies will be conducted to generate human-mouse cell hybrids that retain a single human chromosome for rapid gene mapping purposes. This research is designed to locate human genes associated with molecular disease and cancer to specific chromosomal sites for genetically understanding human disease, gene organization and control, and for genetic diagnosis and counseling.
| Project Number : | 5R01GM020454-15 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA |
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BIOMEDICAL RESEARCH SUPPORT
(1989)
| Project Number : | 2S07RR005493-26 |
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| ICD : | NATIONAL CENTER FOR RESEARCH RESOURCES |
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| IRG : | NSS |
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| Project Terms : | HEALTH SCIENCES RESEARCH, BIOMEDICAL RESEARCH SUPPORT, HOSPITALS CHILDREN |
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AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1988)
Abstract :
Human development is the summation of many individual biochemical processes, each genetically programed to function systematically, leading to the final expression of an enzyme or protein. Certain inherited lysosomal enzyme disorders associated with abnormal development provide excellent models for studying the genetic control of human enzyme expression and cellular localization. The molecular genetics of two groups of unique lysosomal enzyme disorders will be studied. They are the mucolipidoses and the arylsulfatase-A deficiency disorders. Genetic variants indicate that multiple genes with structural, processing, and other functions are altered for both groups. The mucolipidoses consist of mucolipidosis II and III characterized by a G1cNAc-P transferase deficiency that affects the biosynthesis and localization of many lysosomal enzymes. We have identified at least 3 genes that are involved in G1cNAc-P transferase expression. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Evidence suggests perhaps 4 genes involved in the expression of arylsulfatase-A. Somatic cell genetic studies will identify the genes involved in the mucolipidoses and the arylsulfatase-A deficiency disorders. Biochemical, immunological, and molecular studies will characterize each gene. Evidence indicates several types of genes, including structural and processing genes. G1cNAc-P transferase and arylsulfatase-A will be purified and antibodies made. G1cNAc-P transferase and arylsulfatase-A structural genes will be cloned using different alternatives. The cloned probes will be used to determine gene organization; the disease-associated lesions; and gene expression in structural and non-structural gene variants. The biochemical, immunological, and molecular markers, including DNA polymorphisms, produced will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe genes involved in the expression of lysosomal enzymes, which will contribute basic information for human development and genetics.
| Project Number : | 5R01HD005196-16 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, PROTEINS BIOSYNTHESIS, SULFATASES, ARYLSULFATASES, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, DISEASES, MOLECULAR LEVEL STUDIES (GENERAL), ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, OPERON, STRUCTURAL GENE, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, genetic manipulation GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
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AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1988)
Abstract :
Human development is the summation of many individual biochemical processes, each genetically programed to function systematically, leading to the final expression of an enzyme or protein. Certain inherited lysosomal enzyme disorders associated with abnormal development provide excellent models for studying the genetic control of human enzyme expression and cellular localization. The molecular genetics of two groups of unique lysosomal enzyme disorders will be studied. They are the mucolipidoses and the arylsulfatase-A deficiency disorders. Genetic variants indicate that multiple genes with structural, processing, and other functions are altered for both groups. The mucolipidoses consist of mucolipidosis II and III characterized by a G1cNAc-P transferase deficiency that affects the biosynthesis and localization of many lysosomal enzymes. We have identified at least 3 genes that are involved in G1cNAc-P transferase expression. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Evidence suggests perhaps 4 genes involved in the expression of arylsulfatase-A. Somatic cell genetic studies will identify the genes involved in the mucolipidoses and the arylsulfatase-A deficiency disorders. Biochemical, immunological, and molecular studies will characterize each gene. Evidence indicates several types of genes, including structural and processing genes. G1cNAc-P transferase and arylsulfatase-A will be purified and antibodies made. G1cNAc-P transferase and arylsulfatase-A structural genes will be cloned using different alternatives. The cloned probes will be used to determine gene organization; the disease-associated lesions; and gene expression in structural and non-structural gene variants. The biochemical, immunological, and molecular markers, including DNA polymorphisms, produced will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe genes involved in the expression of lysosomal enzymes, which will contribute basic information for human development and genetics.
| Project Number : | 3R01HD005196-16S1 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, PROTEINS BIOSYNTHESIS, SULFATASES, ARYLSULFATASES, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, DISEASES, MOLECULAR LEVEL STUDIES (GENERAL), ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, OPERON, STRUCTURAL GENE, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, genetic manipulation GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1987)
Abstract :
Human development is the summation of many individual biochemical processes, each genetically programed to function systematically, leading to the final expression of an enzyme or protein. Certain inherited lysosomal enzyme disorders associated with abnormal development provide excellent models for studying the genetic control of human enzyme expression and cellular localization. The molecular genetics of two groups of unique lysosomal enzyme disorders will be studied. They are the mucolipidoses and the arylsulfatase-A deficiency disorders. Genetic variants indicate that multiple genes with structural, processing, and other functions are altered for both groups. The mucolipidoses consist of mucolipidosis II and III characterized by a G1cNAc-P transferase deficiency that affects the biosynthesis and localization of many lysosomal enzymes. We have identified at least 3 genes that are involved in G1cNAc-P transferase expression. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Evidence suggests perhaps 4 genes involved in the expression of arylsulfatase-A. Somatic cell genetic studies will identify the genes involved in the mucolipidoses and the arylsulfatase-A deficiency disorders. Biochemical, immunological, and molecular studies will characterize each gene. Evidence indicates several types of genes, including structural and processing genes. G1cNAc-P transferase and arylsulfatase-A will be purified and antibodies made. G1cNAc-P transferase and arylsulfatase-A structural genes will be cloned using different alternatives. The cloned probes will be used to determine gene organization; the disease-associated lesions; and gene expression in structural and non-structural gene variants. The biochemical, immunological, and molecular markers, including DNA polymorphisms, produced will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe genes involved in the expression of lysosomal enzymes, which will contribute basic information for human development and genetics.
| Project Number : | 5R01HD005196-15 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, PROTEINS BIOSYNTHESIS, SULFATASES, ARYLSULFATASES, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, DISEASES, MOLECULAR LEVEL STUDIES (GENERAL), ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, OPERON, STRUCTURAL GENE, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, genetic manipulation GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1987)
Abstract :
Human development is the summation of many individual biochemical processes, each genetically programed to function systematically, leading to the final expression of an enzyme or protein. Certain inherited lysosomal enzyme disorders associated with abnormal development provide excellent models for studying the genetic control of human enzyme expression and cellular localization. The molecular genetics of two groups of unique lysosomal enzyme disorders will be studied. They are the mucolipidoses and the arylsulfatase-A deficiency disorders. Genetic variants indicate that multiple genes with structural, processing, and other functions are altered for both groups. The mucolipidoses consist of mucolipidosis II and III characterized by a G1cNAc-P transferase deficiency that affects the biosynthesis and localization of many lysosomal enzymes. We have identified at least 3 genes that are involved in G1cNAc-P transferase expression. The arylsulfatase-A deficiency disorders consist of metachromatic leukodystrophy, the multiple sulfatase deficiency disorder, the pseudo deficiency disorder, and the activator deficient disorder. Arylsulfatase-A is also deficient in the mucolipidoses. Evidence suggests perhaps 4 genes involved in the expression of arylsulfatase-A. Somatic cell genetic studies will identify the genes involved in the mucolipidoses and the arylsulfatase-A deficiency disorders. Biochemical, immunological, and molecular studies will characterize each gene. Evidence indicates several types of genes, including structural and processing genes. G1cNAc-P transferase and arylsulfatase-A will be purified and antibodies made. G1cNAc-P transferase and arylsulfatase-A structural genes will be cloned using different alternatives. The cloned probes will be used to determine gene organization; the disease-associated lesions; and gene expression in structural and non-structural gene variants. The biochemical, immunological, and molecular markers, including DNA polymorphisms, produced will be available for genetic counseling, population screening, gene mapping, and diagnosis. These studies will describe genes involved in the expression of lysosomal enzymes, which will contribute basic information for human development and genetics.
| Project Number : | 2R01HD005196-14 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, PROTEINS BIOSYNTHESIS, SULFATASES, ARYLSULFATASES, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, DISEASES, MOLECULAR LEVEL STUDIES (GENERAL), ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS DIAGNOSIS, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, BIOCHEMICAL GENETICS, MOLECULAR CLONING, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENES, OPERON, STRUCTURAL GENE, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, genetic manipulation GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1986)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 2R01GM020454-09 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), CELL HYBRIDS, ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA, VIRUSES, PAPOVAVIRIDAE, POLYOMAVIRUS, SV40 VIRUS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1986)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-10 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), CELL HYBRIDS, ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA, VIRUSES, PAPOVAVIRIDAE, POLYOMAVIRUS, SV40 VIRUS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1986)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-11 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), CELL HYBRIDS, ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA, VIRUSES, PAPOVAVIRIDAE, POLYOMAVIRUS, SV40 VIRUS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1986)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-12 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA, VIRUSES, PAPOVAVIRIDAE, POLYOMAVIRUS, SV40 VIRUS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1986)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-13 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | MGN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, MAMMALIAN GENETICS STUDY SECTION, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, BIOCHEMICAL GENETICS, GENETIC CODING, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, CYTOGENETICS, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS STRUCTURE, NUCLEOSIDES (TIDES) SEQUENCE, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation BACTERIA, ENTEROBACTERIACEAE, ESCHERICHIA COLI, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS, VIRUSES, BACTERIOPHAGE LAMBDA, VIRUSES, PAPOVAVIRIDAE, POLYOMAVIRUS, SV40 VIRUS |
|---|
POSTDOCTORAL PROGRAM IN MAMMALIAN BIOCHEMICAL GENETICS
(1986)
| Project Number : | 5T32GM007093-10 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GBD |
|---|
MAMMALIAN BIOCHEMICAL GENETICS
(1985)
| Project Number : | 5T32GM007093-07 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GBD |
|---|
MAMMALIAN BIOCHEMICAL GENETICS
(1985)
| Project Number : | 5T32GM007093-08 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GBD |
|---|
POSTDOCTORAL PROGRAM IN MAMMALIAN BIOCHEMICAL GENETICS
(1985)
| Project Number : | 5T32GM007093-09 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GBD |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1984)
Abstract :
Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes, proteins, and differentiated products as an approach to reducing to experimental dimensions human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of such essential products. Enzymes, proteins, and differentiated products will be studied that depend on several genes for their final expression and, when altered, result in abnormal development and severe inherited disease. The genetic dissection and chromosome mapping of genes necessary for the final realization of these products will be studied using normal and deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. A genetic dissection and chromosome mapping of molecular disorders using somatic cell hybrids will provide a better understanding of metabolic diseases which are often fatal and will determine what type of gene is abnormal and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.
| Project Number : | 5R01HD005196-10 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS STUDY SECTION, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GROWTH AND DEVELOPMENT, PROTEINS BIOSYNTHESIS, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1984)
Abstract :
Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes, proteins, and differentiated products as an approach to reducing to experimental dimensions human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of such essential products. Enzymes, proteins, and differentiated products will be studied that depend on several genes for their final expression and, when altered, result in abnormal development and severe inherited disease. The genetic dissection and chromosome mapping of genes necessary for the final realization of these products will be studied using normal and deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. A genetic dissection and chromosome mapping of molecular disorders using somatic cell hybrids will provide a better understanding of metabolic diseases which are often fatal and will determine what type of gene is abnormal and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.
| Project Number : | 5R01HD005196-11 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS STUDY SECTION, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GROWTH AND DEVELOPMENT, PROTEINS BIOSYNTHESIS, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1984)
Abstract :
Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes, proteins, and differentiated products as an approach to reducing to experimental dimensions human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of such essential products. Enzymes, proteins, and differentiated products will be studied that depend on several genes for their final expression and, when altered, result in abnormal development and severe inherited disease. The genetic dissection and chromosome mapping of genes necessary for the final realization of these products will be studied using normal and deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. A genetic dissection and chromosome mapping of molecular disorders using somatic cell hybrids will provide a better understanding of metabolic diseases which are often fatal and will determine what type of gene is abnormal and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.
| Project Number : | 5R01HD005196-12 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS STUDY SECTION, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GROWTH AND DEVELOPMENT, PROTEINS BIOSYNTHESIS, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, SULFATASES, ARYLSULFATASES, genetic manipulation GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1984)
Abstract :
Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes, proteins, and differentiated products as an approach to reducing to experimental dimensions human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of such essential products. Enzymes, proteins, and differentiated products will be studied that depend on several genes for their final expression and, when altered, result in abnormal development and severe inherited disease. The genetic dissection and chromosome mapping of genes necessary for the final realization of these products will be studied using normal and deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. A genetic dissection and chromosome mapping of molecular disorders using somatic cell hybrids will provide a better understanding of metabolic diseases which are often fatal and will determine what type of gene is abnormal and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.
| Project Number : | 5R01HD005196-13 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS STUDY SECTION, GENETICS, DEVELOPMENTAL GENETICS, GENETICS, GENES, GENE EXPRESSION, GROWTH AND DEVELOPMENT, PROTEINS BIOSYNTHESIS, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS INBORN DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, SULFATASES, ARYLSULFATASES, genetic manipulation HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1984)
Abstract :
Human somatic cell genetic research is proposed to dissect and assign to chromosomes the different numbers and kinds of genes necessary for the final expression of enzymes and proteins as an approach to reducing to experimental dimensions of human development and metabolic disease. Using the somatic cell hybrid methodology, structural genes, post-translational modification genes, regulatory genes, subcellular localization genes, and assembly genes will be described that function in the biogenesis of enzymes and proteins. These studies will involve the genetic characterization of lysosomal enzymes, enzymes in amino acid metabolism, adenosine deaminase in purine metabolism, the immunoglobuins, and H1 histone proteins in chromatin assembly. These proteins were chosen since several genes are involved in their final expression and, when altered, abnormal development and severe inherited disease result. The genetic dissection and chromosome mapping of these essential enzymes and proteins will be studied using normal and enzyme-deficient human cultured cells in cell hybrid or heterokaryon combinations with either human or rodent cells. Enzyme-deficient fibroblasts to be used are associated with neurodegenerative diseases such as Tay-Sachs, Sandhoff-Jatzkewitz, metachromatic leukodystrophy, and GM1 gangliosidosis; with aminoacidopathies such as argininosuccinic aciduria, cystathionuria, and homocystinuria; and with immune diseases such as severe combined immunodeficiency disease and other immunoglobulin disorders. A genetic dissection and chromosome mapping of these disorders using somatic cell hybrids will provide a better molecular understanding of these often fatal diseases, what type of gene is abnormal, and how it relates to abnormal development. Such genetic information will undoubtedly aid in genetic counseling and prenatal diagnosis. Assignment of these genes will contribute to understanding the organization of the human genome as it relates to essential biological molecules, to human development, and to molecular disease.
| Project Number : | 2R01HD005196-09 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, ENZYMES, GENETICS STUDY SECTION, GENETICS, GENES, GENE EXPRESSION, GROWTH AND DEVELOPMENT, PROTEINS BIOSYNTHESIS, genetic mapping AMINO ACIDS METABOLISM (GENERAL), AMINOHYDROLASES, ADENOSINE DEAMINASE, CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, ENZYMES, ISOENZYMES, GENETIC DISORDERS, GENETIC COUNSELING, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, CHROMATIN, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOPATHOLOGY, IMMUNOLOGIC DEFICIENCY DISORDERS, METABOLIC DISORDERS DIAGNOSIS, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, NUCLEOPROTEINS, HISTONES, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PREGNANCY, ANTEPARTUM DIAGNOSIS, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1981)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrid growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes will be mapped that code for some 60 enzymes, as well as plasma membrane proteins, ribosomal proteins, and viral characteristics. The enzymes are associated with inherited diseases including hemolytic anemias and neurodegenerative disorders, the lysosome, essential metabolic pathways, and aspects of development. The plasma membrane proteins, ribosomal proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relatonships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-06 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES) HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1981)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrid growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes will be mapped that code for some 60 enzymes, as well as plasma membrane proteins, ribosomal proteins, and viral characteristics. The enzymes are associated with inherited diseases including hemolytic anemias and neurodegenerative disorders, the lysosome, essential metabolic pathways, and aspects of development. The plasma membrane proteins, ribosomal proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relatonships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-07 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES) HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1981)
Abstract :
Research is proposed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes involving 20 of the 24 different chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes will be mapped that code for some 60 enzymes, as well as plasma membrane proteins, ribosomal proteins, and viral characteristics. The enzymes are associated with inherited diseases incluing hemolytic anemias and neurodegenerative disorders, the lysosome, essential metabolic pathways, and aspects of development. The plasma membrane proteins, ribosomal proteins, lysomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetics disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 2R01GM020454-04 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CELL FUSION (GENERAL), CELL SURFACE ACTIVITY (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), neoplastic growth HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS*, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY)*, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1981)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes involving 20 of the 24 different chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes will be mapped that code for some 60 enzymes, as well as plasma membrane proteins, ribosomal proteins, and viral characteristics. The enzymes are associated with inherited diseases including hemolytic anemias and neurodegenerative disorders, the lysosome, essential metabolic pathways, and aspects of development. The plasma membrane proteins, ribosomal proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man. BIBLIOGRAPHIC REFERENCES: Chapman, V. M., and Shows, T. B. 1976. Somatic cell genetic evidence for X-chromosomes linkage of three enzymes in the mouse. Nature 259:665-667. Evans, J. T., Shows, T. B., Sproul, E. E., Paolini, N. S., Mittelman, A., and Hauschka, T. S. 1977. Genetics of colon carcinogenesis in mice treated with 1,2-dimethylhydrazine (DMH). Cancer Research 37:134-136.
| Project Number : | 5R01GM020454-05 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES) HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS*, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY)*, NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
|---|
HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1981)
Abstract :
Research will be performed to determine gene linkage relationships and the chromosome assignment and location of human genes associated with essential cellular functions and metabolic disease. Realization of a detailed human gene map can be accomplished utilizing man-rodent somatic cell hybrids growing in tissue culture as an alternative to classical Mendelian studies. Since human chromosomes are lost in man-rodent cell hybrids, gene linkages and chromosome assignments can be determined by correlating the presence or loss of human genes and chromosomes in hybrid cells. Human gene localization to regions and subregions of chromosomes will be accomplished in cell hybrids by utilizing human parental cell lines with translocated chromosomes. These altered chromosomes will provide for the subdivision of chromosomes which facilitates the detailed mapping of human genes. Human genes that are being mapped and regionally mapped include some 60 enzymes, as well as external membrane proteins, cytoplasmic proteins, viral characteristics, and nucleotide segments using cloned genes and the recombinant DNA technology. The enzymes are associated with inherited diseases including hemolytic anemias, neurodegenerative disorders and the aminoacidopathies, essential metabolic pathways, and aspects of development. The external membrane proteins, lysosomal enzymes, and viral characteristics all function as part of a structure or cellular organelle. The DNA segments for mapping will encode several hormones, RNA, and enzyme genes. Comparative mapping of the mouse will be studied to predict chromosome assignments of human genes. A linear order and detailed map of human genes will provide a better understanding of the organization of the human genome. In addition to linkage relationships useful in genetic testing, counseling, and prenatal diagnosis, this information should provide insights into control of gene expression; assembly of complex molecules, cellular organelles and structures; aspects of genetic disease; genetic relationships; chromosomal location and gene function; and the evolution of the human genome. Such knowledge will be necessary for understanding the genetic biology of man.
| Project Number : | 5R01GM020454-08 |
|---|
| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
|---|
| IRG : | GEN |
|---|
| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, MEMBRANE SURFACE (BIOLOGICAL) ACTIVITY (GENERAL), NUCLEIC ACIDS SYNTHESIS, DNA, NUCLEIC ACIDS SYNTHESIS, RNA, NUCLEIC ACIDS, DNA RIBOSOMAL, NUCLEIC ACIDS, RRNA, PROTEINS BIOSYNTHESIS, TRANSFERASES, VIRUSES, ONCOGENIC (INCLUDING ONCOGENIC VIRUS-LIKE PARTICLES), genetic manipulation HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, MAMMALS, RODENTS, MYOMORPHA, HAMSTERS, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), NEOPLASMS OF BLOOD AND RE SYSTEM, LYMPHOMA, BURKITT'S, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1979)
Abstract :
This project is designed to (a) identify human genes which are important in the control of gene expression and to (b) determine gene linkage relationships of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. Many of these studies involve the genetic characterization of a group of acid hydrolases associated with lysosomes. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay-Sachs disease, Sandhoff-Jatzkewitz disease, metachromatic leukodystrophy and generalized gangliosidosis. These studies are designed to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies and hopefully, to aid in the prenatal diagnosis of lysosomal storage diseases. It is hoped that such information will help to construct models of lysosomal biogenesis and regulation. Proliferating man-mouse somatic cell hybrids are particularly suited for this study since human chromosomes but not mouse chromosomes are lost, which provides the mechanism to identify human genes and linkage relationships if human and mouse gene markers can be distinguished. The mapping of human genes to linkage groups requires a large number of markers. It is planned to increase our present catalogue from about 30 human enzyme markers to 50 markers by optimizing procedures for new enzymes, ribosomal proteins and membrane proteins. These data will increase the chances of placing a biochemical marker on each human chromosome.
| Project Number : | 5R01HD005196-05 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, GENETIC CODING, genetic mapping CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, GENES, GENE EXPRESSION, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM 2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PROTEINS BIOSYNTHESIS, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS*, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, MICE*, MAMMALS, RODENTS, HAMSTERS*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1979)
Abstract :
This project is designed to (a) identify human genes which are important in the control of gene expression and to (b) determine gene linkage relationships of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. Many of these studies involve the genetic characterization of a group of acid hydrolases associated with lysosomes. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sandhoff-Jatzkewitz disease, metachromatic leukodystrophy and generalized gangliosidosis. These studies are designed to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies and, hopefully, to aid in the prenatal diagnosis of lysosomal storage diseases. It is hoped that such information will help to construct models of lysosomal biogenesis and regulation. Proliferating man-mouse somatic cell hybrids is particulary suited for this study since human chromosomes but not mouse chromosomes are lost which provides the mechanism for dissecting the genetic components necessary for the final expression of a lysosomal enzyme. BIBLIOGRAPHIC REFERENCES: Shows, T. B. 1975. Genetics, expression, and characterization of isozymes in somatic cell hybrids. Isozymes, III. Developmental Biology, p. 619 (Academic Press). Shows, T. B. 1975. Gene markers for mapping the human genome: The 1974 listing. Cytogenet. and Cell Genet. 14:29-37.
| Project Number : | 5R01HD005196-06 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, GENETIC CODING, genetic mapping CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, GENES, GENE EXPRESSION, GENETICS, SOMATIC CELL AND TRANSFORMATION, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM 2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS*, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY)*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1979)
Abstract :
This project is designed to (a) elucidate human genes which are important in the control of gene expression and to (b) determine gene linkage relationships of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. Many of these studies involve the genetic characterization of a group of acid hydrolases associated with lysosomes. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sanhoff-Jatzkewitz disease, metachromatic leukodystrophy, and generalized gangliosidosis. These studies are designed to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies and, hopefully, to aid in the prenatal diagnosis of lysosomal storage diseases. It is anticipated that such information will help to construct models of lysosomal biogenesis and regulation. Proliferating man-mouse somatic cell hybrids are particularly suited for this study since human chromosomes, but not mouse chromosomes, are lost which provides the mechanism to identify human genes and linkage relationships if human and mouse gene markers can be distinguished. The mapping of human genes to linkage groups requires a large number of markers. It is planned to increase our present catalogue from about 30 human enzyme markers to 50 markers by optimizing procedures for new enzymes, ribosomal proteins, and membrane proteins. These data will increase the chances of placing a biochemical marker on each human chromosome. BIBLIOGRAPHIC REFERENCES: Lalley, P.A., Brown, J.A., Eddy, R.L., Haley, L.L., Byers, M.G., Goggin, A., and Shows, T.B. 1977. Human Beta-glucuronidase: Assignment of the structural gene to chromosome 7 using somatic cell hybrids. Biochem. Genetics 15 (in press). Champion, M.J., and Shows, T.B. 1977. Electrophoretic abnormalities of lysosomal enzymes in mucolipidosis fibroblast lines. Am. J. Human Genet. (in press).
| Project Number : | 5R01HD005196-07 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, GENES, GENE EXPRESSION, genetic mapping CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM 2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS*, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY)*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1979)
Abstract :
This project is designed to (a) elucidate human genes which are important in the control of gene expression and to (b) determine the genetic organization of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. These studies involve the genetic characterization of a group of acid hydrolases associated with lysomones. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sandhoff-Jatzhewitz disease, metachromatic leukodystrophy, generalized gangliosidosis, Fabry's disease, and fucosidosis. These studies are deigned to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies which result in fatal childhood diseases and, hopefully, to aid in the diagnosis, prenatal detection, and treatment of lysosomal storage diseases. It is anticipated that such information will be necessary for the construction of models of lysosomal biogenesis and regulation which are imporant aspects of human development. Proliferating man-mouse somatic cell hybrids are particularly suited for this study since human chromosomes, but not mouse chromosomes, are lost which provides the mechanism to identify human genes and linkage relationships. The mapping of human genes to linkage groups requires a large number of markers. It is planned to increase our present catalogue from about 40 human enzyme markers to 60 markers by optimizing procedures for new enzymes, ribosomal proteins, and membrane proteins. These data will increase the chances of placing genes associated with development on each human chromosome.
| Project Number : | 5R01HD005196-08 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, GENES, GENE EXPRESSION, genetic mapping CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, CELL FUSION (GENERAL), CELL HYBRIDS, CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE INTERACTION, COMPLEMENTATION, GENETICS, GENETIC CODING, GENETICS, SOMATIC CELL AND TRANSFORMATION, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, MUCOPOLYSACCHARIDOSIS, LIPOMUCOPOLYSACCHARIDOSIS, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM 2 TYPE I, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, SULFATASES, ARYLSULFATASES GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, GENETICS, MUTATION, MUTANTS, HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE, MAMMALS, RODENTS, MYOMORPHA, MICE (LABORATORY), PHYSICAL SEPARATION, ELECTROPHORESIS, GEL, TISSUE (CELL) CULTURE, CLONE CELLS |
|---|
AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1979)
Abstract :
This project is designed to (a) elucidate human genes which are important in the control of gene expression and to (b) determine gene linkage relationships of these and other gene markers. These aspects of human development will be studied in a parasexual genetic way employing man-mouse somatic cell hybrids. Many of these studies involve the genetic characterization of a group of acid hydrolases associated with lysosomes. Genes important in the final expression of lysosomal hydrolases will be studied employing normal and enzyme deficient human fibroblasts in hybrid combinations with mouse cells. Several of the enzymes are associated with such neurodegenerative diseases as Tay Sachs disease, Sandhoff-Jatzkewitz disease, metachromatic leukodystrophy and generalized gangliosidosis. These studies are designed to provide a better understanding of the genetics of lysosomal enzymes and their deficiencies and hopefully, to aid in the prenatal diagnosis of lysosomal storage diseases. It is hoped that such information will help to construct models of lysosomal biogenesis and regulation. Proliferating man-mouse somatic cell hybrids are particularly suited for this study since human chromosomes, but not mouse chromosomes are lost which provides the mechanism to identify human genes and linkage relationships if human and mouse gene markers can be distinguished. The mapping of human genes to linkage groups requires a large number of markers. It is planned to increase our present catalogue from about 30 human enzyme markers to 50 markers by optimizing procedures for new enzymes, ribosomal proteins and membrane proteins. These data will increase the chances of placing a biochemical marker on each human chromosome.
| Project Number : | 2R01HD005196-04 |
|---|
| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
|---|
| IRG : | GEN |
|---|
| Project Terms : | ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, GENETIC CODING, GENETICS, GENETIC REGULATION, GENETIC INDUCTION-REPRESSION-DEREPRESSION CARBOHYDRASES, BETA-GLUCURONIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL COMPONENTS, LYSOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, MUTATION, METABOLIC DISORDERS INBORN, LEUKODYSTROPHIES, METACHROMATICLEUCOENCEPHALOPATHY, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM1, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE, PHOSPHOMONOESTERASES, ACID PHOSPHATASE, PROTEINS BIOSYNTHESIS, cell differentiation, genetic mapping CELL COMPONENTS, RIBOSOMES, CELL HYBRIDS, HETEROKARYON, CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETICS, SOMATIC CELL AND TRANSFORMATION, HUMAN, NONCLINICAL*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, MICE*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
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HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1976)
| Project Number : | 1R01GM020454-01 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| IRG : | GEN |
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| Project Terms : | GENETIC DISORDERS, CHROMOSOME ABNORMALITIES, GENETIC MAPPING AND MARKERS, GENETICS, CHROMOSOME TRANSLOCATIONS, HYDROLASES, ISOMERASES, OXIDOREDUCTASES, TRANSFERASES BLOOD AND RE DISORDERS, ANEMIA HEMOLYTIC CONGENITAL (GENERAL), CELL HYBRIDS, HETEROKARYON, CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETICS STUDY SECTION, GENETICS, SEX CHROMOSOMES HUMAN, NONCLINICAL*, MAMMALS, MICE*, MAMMALS, RODENTS, HAMSTERS*, TISSUE (CELL) CULTURE* |
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HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1976)
Abstract :
The assignment of human genes to chromosomes has proved difficult when limited to classical Mendelian genetics. A parasexual alternative to conventional methods has been demonstrated by the use of interspecific somatic cell hybrids. Human chromosomes are preferentially lost in proliferating man-mouse and man-Chinese hamster cell hybrids and clones can be isolated with different numbers and combinations of human chromosomes and enzymes. Human gene-chromosome relationships are established when positive correlations are observed for the concurrent loss of specific enzymes and chromosomes. The objective for this proposed research is to assign human genes to chromosomes and, by employing human translocated chromosomes, to map genes to specific segments of human chromosomes. A series of human cells possessing individual translocations involving chromosomes 1, 2, 3, 6, 9, 13, 14, 18, 20, 21, 22, and X will be hybridized to mouse and to Chinese hamster cells. The positive association of two linkage groups and a translocated chromosome can lead to the assignment of genes to specific chromosomes and in fact, to a specific segment of a chromosome. Human chromosomes will be identified by fluorescence and Giemsa banding and heterochromatin staining. Some 40 human enzymes will be tested in the cell hybrids. Several of the enzymes are associated with inherited metabolic diseases including hemolytic anemias and neurodegenerative disorders. The evolutionary significance of human gene linkages will be studied by comparing the gene linkages of other species as determined through interspecific cell hybrids. The expression of translocated genes and a study of the inactive X hypothesis will be investigated with X-autosomal translocations in cell hybrids. A knowledge of gene assignments in man, how the genes are controlled, and why they are coded on a specific chromosome necessary for understanding the biology of man.
| Project Number : | 5R01GM020454-02 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| IRG : | GEN |
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| Project Terms : | CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping BLOOD AND RE DISORDERS, ANEMIA HEMOLYTIC CONGENITAL (GENERAL), CONNECTIVE TISSUE CELLS, FIBROBLASTS, GENETIC DISORDERS, CHROMOSOME ABNORMALITIES, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENES, GENE EXPRESSION, GENETICS, GENETIC CODING, HYDROLASES, ISOMERASES, NEUROLOGIC MANIFESTATIONS, OXIDOREDUCTASES, TISSUE (CELL) CULTURE, CLONE CELLS*, TRANSFERASES HUMAN, NONCLINICAL*, MAMMALS, MICE*, MAMMALS, RODENTS, HAMSTERS* |
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HUMAN GENE LINKAGE RELATIONSHIPS IN CELL HYBRIDS
(1976)
Abstract :
The assignment of human genes to chromosomes has proved difficult when limited to classical Mendelian genetics. A parasexual alternative to conventional methods has been demonstrated by the use of interspecific somatic cell hybrids. Human chromosomes are preferentially lost in proliferating man-mouse and man-Chinese hamster cell hybrids and clones can be isolated with different numbers and combinations of human chromosomes and enzymes. Human gene-chromosome relationships are established when positive correlations are observed for the concurrent loss of specific enzymes and chromosomes. The objective for this proposed research is to assign human genes to chromosomes and, by employing human translocated chromosomes, to map genes to specific segments of human chromosomes. A series of human cells possessing individual translocations involving chromosomes 1, 2, 3, 6, 9, 13, 14, 18, 20, 21, 22, and X will be hybridized to mouse and to Chinese hamster cells. The positive association of two linkage groups and a translocated chromosome can lead to the assignment of genes to specific chromosomes and in fact, to a specific segment of a chromosome. Human chromosomes will be identified by fluorescence and Giemsa banding and heterochromatin staining. Some 40 human enzymes will be tested in the cell hybrids. Several of the enzymes are associated with inherited metabolic diseases including hemolytic anemias and neurodegenerative disorders. The evolutionary significance of human gene linkages will be studied by comparing the gene linkages of other species as determined through interspecific cell hybrids. The expression of translocated genes and a study of the inactive X hypothesis will be investigated with X-autosomal translocations in cell hybrids. A knowledge of gene assignments in man, how the genes are controlled, and why they are coded on a specific chromosome necessary for understanding the biology of man.
| Project Number : | 5R01GM020454-03 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| IRG : | GEN |
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| Project Terms : | CELL HYBRIDS, HETEROKARYON, GENETIC MAPPING, LINKAGE, GENETICS STUDY SECTION, GENETICS, MUTATION, CHROMOSOME MUTATION, CHROMOSOME TRANSLOCATIONS, genetic mapping CARBOHYDRASES, ALPHA-GALACTOSIDASE, CARBOHYDRASES, HEXOSAMINIDASES, CELL FUSION (GENERAL), ENZYME MECHANISMS, GENETIC MAPPING, GENETIC MARKERS, GENETICS, CHROMOSOMES, SEX CHROMOSOMES, GENETICS, GENETIC CODING, TISSUE (CELL) CULTURE, CLONE CELLS*, TRANSFERASES HUMAN, TISSUES, FLUIDS ETC. FROM NON-RELATED SOURCES OUTSIDE IMMEDIATE PROJECT*, MAMMALS, MICE*, MAMMALS, RODENTS, HAMSTERS*, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, GANGLIOSIDE GM2 TYPE II, METABOLIC DISORDERS INBORN, SPHINGOLIPIDOSES, TRIHEXOSIDE |
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AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1974)
| Project Number : | 5R01HD005196-02 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | GEN |
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| Project Terms : | CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, GENETIC MAPPING AND MARKERS, GENETICS, GENE EXPRESSION, GENETICS, GENETIC INDUCTION-REPRESSION, PROTEINS BIOSYNTHESIS, cell differentiation BLOOD CELLS, LYMPHOBLASTS, CELL COMPONENTS, LYSOSOMES, CELL COMPONENTS, RIBOSOMES, GENETICS STUDY SECTION, GENETICS, MUTATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULINS, IMMUNOGENETICS (GENERAL), NUCLEIC ACIDS, RRNA HUMAN, NONCLINICAL*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, MICE*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
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AN APPROACH TO HUMAN DEVELOPMENT WITH CELL HYBRIDS
(1974)
| Project Number : | 5R01HD005196-03 |
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| ICD : | EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT |
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| IRG : | GEN |
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| Project Terms : | CELL HYBRIDS, HETEROKARYON, ENZYME MECHANISMS, GENETIC MAPPING AND MARKERS, GENETICS, GENE EXPRESSION, GENETICS, GENETIC INDUCTION-REPRESSION, PROTEINS BIOSYNTHESIS, cell differentiation BLOOD CELLS, LYMPHOBLASTS, CELL COMPONENTS, LYSOSOMES, CELL COMPONENTS, RIBOSOMES, GENETICS STUDY SECTION, GENETICS, MUTATION, GLOBULINS, GAMMA GLOBULINS, IMMUNOGLOBULIN(S), IMMUNOGENETICS (GENERAL), NUCLEIC ACIDS, RRNA HUMAN, NONCLINICAL*, IMMUNOLOGICAL TESTS AND IMMUNOASSAY, IMMUNOFLUORESCENCE*, MAMMALS, MICE*, PHYSICAL SEPARATION, ELECTROPHORESIS, GEL*, TISSUE (CELL) CULTURE, CLONE CELLS* |
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SOMATIC CELL GENETICS OF LYSOSOMAL ENZYMES
(1973)
| Project Number : | 5P01GM019521-020006 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| Project Terms : | CELL COMPONENTS, LYSOSOMES, GENETICS, MUTATION, GENETICS, SOMATIC CELL AND TRANSFORMATION CARBOHYDRASES, BETA-GALACTOSIDASE, CELL HYBRIDS, GENETICS, RECOMBINATION, GROWTH MEDIA, DEFICIENT, METABOLIC DISORDERS INBORN, TISSUE (CELL) CULTURE* HUMAN, NONCLINICAL*, MAMMALS, MICE* |
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SOMATIC CELL GENETICS OF LYSOSOMAL ENZYMES
(1972)
| Project Number : | 1P01GM019521-010006 |
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| ICD : | NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES |
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| Project Terms : | CELL COMPONENTS, LYSOSOMES, GENETICS, MUTATION, GENETICS, SOMATIC CELL AND TRANSFORMATION CARBOHYDRASES, BETA-GALACTOSIDASE, CELL HYBRIDS, GENETICS, RECOMBINATION, GROWTH MEDIA, DEFICIENT, METABOLIC DISORDERS INBORN, TISSUE (CELL) CULTURE* HUMAN, NONCLINICAL*, MAMMALS, MICE* |
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